Prostate cancer is the most common cancer in American men and is second only to lung cancer as a cause of cancer death among men, yet little is known about what reduces the likelihood of its recurrence after initial treatment. The discovery of safe, effective therapies for high-risk patients is of major importance. Recently, results from several studies have suggested that cholesterol-lowering statins-which reduce overall mortality by decreasing fatal heart attacks and strokes-may also be effective against cancer. Our research team and several others have reported an inverse association between statin use and prostate cancer incidence. Importantly, the greatest reduction in risk was for high grade, advanced stage, and fatal prostate cancers. Our study aims to investigate whether statins have a beneficial effect on patients undergoing treatment for prostate cancer. We hypothesize that many of the mechanisms involved in statins' altering risk of developing high grade disease are also important in determining risk of cancer recurrence, and that men prescribed statins prior to or shortly following treatment for their initial prostate cancer diagnosis will have reduced risk of its recurrence. We propose to conduct a retrospective longitudinal analysis of data from the Kaiser Permanente Northwest health care system and the Veterans Health Administration; these two health systems have extensive electronic data on more than 5,000 prostate cancer cases that were diagnosed after statin use became common. We propose to: 1) Determine the association between the risk of recurrence of prostate cancer-measured both biochemically and clinically-and the use of statins before and after prostate cancer diagnosis. 2) Explore whether the association between statin use and prostate cancer recurrence varies by primary treatment type (surgery, radiation, or active surveillance). 3) Compare the databases of our two organizations to develop and refine methods for combining data to increase statistical power. We will use propensity score modeling and Cox regression analysis to evaluate these questions, adjusting for pathologic and clinical factors as appropriate. Outcomes from this study could lead to clinical trials and the eventual development of effective and safe adjuvant (secondary) therapy for the reduction of prostate cancer recurrence after initial therapy. Because statins are already in use, new findings about their role in cancer can translate quickly into clinical practice. PUBLIC HEALTH RELEVANCE: Prostate cancer is second only to lung cancer as a cause of cancer death among men, yet little is known about what prevents its recurrence. Our study will investigate whether statins, drugs widely used to lower cholesterol and prevent heart attack and stroke, may also benefit patients who are being treated for prostate cancer. We will analyze more than 5,000 patients' electronic medical records from the Kaiser Permanente Northwest health care system and the Veterans Administration; these two systems have extensive electronic data that will allow us to examine prostate cancer cases that were diagnosed after statin use became common. Our results could lead to clinical trials and the eventual development of effective and safe therapy that helps prevent and reduce prostate cancer recurrence after initial therapy. Because statins are already in use, new findings about their role in cancer could translate quickly into practice.